Self-reactive and transplacental-acquired maternal T cells in SCID patients—time to update
Abstract
Patients with severe combined immunodeficiency (SCID) typically present with profoundly reduced T cells. In some cases, however, T cells may be affected by defects that allow some T-cell development but compromise T-cell function such as in Omenn syndrome (OS), which is characterized by impaired T cell differentiation in the presence of abnormal self-reactive cells. One distinctive feature of SCID patients, which can sometimes resemble the clinical picture of OS, is the presence of alloreactive cells that originated from transplacentally acquired maternal T lymphocytes. The traditional view is that self-reactive cells and transplacentally acquired maternal T cells cannot occur concomitantly in the same OS patient. This review provides an updated functional characterization of transplacentally acquired maternal T cells and compares them with the T cells of an OS patient. An unusual case of an immunodeficient SCID patient with a mild OS phenotype is also presented. This patient had both self-reactive cells and transplacentally acquired maternal T cells, allowing us to simultaneously evaluate the function and tolerance capacities of both cell types. We propose that coexistence of autologous and maternal T cells in patients exhibiting mild OS symptoms was rejected because it had not been studied before and not because the cells are mutually exclusive. Moreover, taking into consideration the milder clinical phenotype associated with transplacentally acquired maternal T cells in SCID patients, we believe that these cells may provide some degree of immunity and prevent autoimmunity, even though they do not actually function to protect against infections.
Statement of novelty: Autologous and transplacental-acquired maternal T cells can coexist in the same SCID patient. Although both cell types are nonfunctional for protecting against infections, maternal cells provide some degree of immunity and therefore are associated with only mild GVHD symptoms.
Formats available
You can view the full content in the following formats:
REFERENCES
Aleman K., Noordzij J.G., De Groot R., Van Dongen J.J., and Hartwig N.G. Reviewing Omenn syndrome Eur. J. Pediatric. 2001 160 12 718 -725
Al-Herz W., Bousfiha A., Casanova J.L., Chatila T., Conley M.E., Cunningham-Rundles C., Etzioni A., Franco J.L., Gaspar H.B., Holland S.M., Klein C., Nonoyama S., Ochs H.D., Oksenhendler E., Picard C., Puck J.M., Sullivan K., and Tang M.L.K. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency Front. Immunol. 2014 5 162
Al-Muhsen S.Z. Delayed presentation of severe combined immunodeficiency due to prolonged maternal T cell engraftment Ann. Saudi. Med. 2010 30 3 239 -242
Amariglio N., Lev A., Simon A., Rosenthal E., Spirer Z., Efrati O., Broides A., Rechavi G., and Somech R. Molecular assessment of thymus capabilities in the evaluation of T-cell immunodeficiency Pediatr. Res. 2010 67 2 211 -216
Appleton A.L., Curtis A., Wilkes J., and Cant A.J. Differentiation of materno-fetal GVGD from Omenn's syndrome in pre-BMT patients with severe combined immunodeficiency Bone Marrow Transpla. 1994 14 1 157 -159
Cassani B., Poliani P.L., Moratto D., Sobacchi C., Marrella V., Imperatori L., Vairo D., Plebani A., Giliani S., Vezzoni P., Facchetti F., Porta F., Notarangelo L.D., Villa A., and Badolato R. Defect of regulatory T cells in patients with Omenn syndrome J. Allergy Clin. Immunol. 2010 125 1 209 -216
Cattaneo F., Recher M., Masneri S., Baxi S.N., Fiorini C., Antonelli F., Wysocki C.A., Calderon J.G., Eibel H., Smith A.R., Bonilla F.A., Tsitsikov E., Giliani S., Notarangelo L.D., and Pai S.-Y. Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment J. Allergy Clin. Immunol. 2013 131 4 1136 -1145
Cavadini P., Vermi W., Facchetti F., Fontana S., Nagafuchi S., Mazzolari E., Sediva A., Marrella V., Villa A., Fischer A., Notarangelo L.D., and Badolato R. AIRE deficiency in thymus of 2 patients with Omenn syndrome J. Clin. Invest. 2005 115 3 728 -732
Cooper M.D., Lanier L.L., Conley M.E., and Puck J.M. Immunodeficiency disorders Hematology Am. Soc. Hematol. Educ. Program. 2003 2003 1 314 -330
Denianke K.S., Frieden I.J., Cowan M.J., Williams M.L., and McCalmont T.H. Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study Bone Marrow Transplant. 2001 28 3 227 -233
Dvorak C.C., Cowan M.J., Logan B.R., Notarangelo L.D., Griffith L.M., Puck J.M., Kohn D.B., Shearer W.T., O'Reilly R.J., Fleisher T.A., Pai S.-Y., Hanson I.C., Pulsipher M.A., Fuleihan R., Filipovich A., Goldman F., Kapoor N., Small T., Smith A., Chan K.-W., Cuvelier G., Heimall J., Knutsen A., Loechelt B., Moore T., and Buckley R.H. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901 J. Clin. Immunol. 2013 33 7 1156 -1164
Kobrynski L.J. and Abramowsky C. Monoclonal IgA gammopathy due to maternal B cells in an infant with severe combined immunodeficiency (SCID) prior to hematopoietic stem cell transplantation J. Pediatr. Hematol. Oncol. 2006 28 1 53 -56
Lev A., Simon A.J., Amariglio N., Rechavi G., and Somech R. Selective clinical and immune response of the oligoclonal autoreactive T cells in Omenn patients after cyclosporin A treatment Clin. Exp. Immunol. 2012a 167 2 338 -345
Lev A., Simon A.J., Ben-Ari J., Takagi D., Stauber T., Trakhtenbrot L., Rosenthal E., Rechavi G., Amariglio N., and Somech R. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency Clin. Exp. Immunol. 2014 176 3 380 -386
Lev A., Simon A.J., Trakhtenbrot L., Goldstein I., Nagar M., Stepensky P., Rechavi G., Amariglio N., and Somech R. Characterizing T cells in SCID patients presenting with reactive or residual T lymphocytes Clin. Dev. Immunol. 2012b 2012 1 -9
Müller S.M., Ege M., Pottharst A., Schulz A.S., Schwarz K., and Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients Blood. 2001 98 1847 -1851
Notarangelo L.D. Partial defects of T-cell development associated with poor T-cell function J. Allergy Clin. Immunol. 2013 131 5 1297 -1305
Notarangelo L.D. Combined immunodeficiencies with nonfunctional T lymphocytes Adv. Immunol. 2014 121 121 -190
Pai S.-Y., Logan B.R., Griffith L.M., Buckley R.H., Parrott R.E., Dvorak C.C., Kapoor N., Hanson I.C., Filipovich A.H., Jyonouchi S., Sullivan K.E., Small T.N., Burroughs L., Skoda-Smith S., Haight A.E., Grizzle A., Pulsipher M.A., Chan K.W., Fuleihan R.L., Haddad E., Loechelt B., Aquino V.M., Gillio A., Davis J., Knutsen A., Smith A.R., Moore T.B., Schroeder M.L., Goldman F.D., Connelly G.A., Porteus M.H., Xiang Q., Shearer W.T., Fleisher T.A., Kohn D.B., Puck J.M., Notarangelo L.D., Cowan M.J., and O'Reilly R.J. Transplantation outcomes for severe combined immunodeficiency, 2000–2009 N. Engl. J. Med. 2014 371 5 434 -446
Palmer K., Green T.D., Roberts J.L., Sajaroff E., Cooney M., Parrott R., Chen D.F., Reinsmoen N.L., and Buckley R.H. Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency J. Allergy Clin. Immunol. 2007 120 2 423 -428
Plebani A., Stringa M., Prigione I., Facchetti P., Ghiotto F., Airoldi I., Giacchino R., Cristina E., Porta F., Grossi C.E., and Pistoia V. Engrafted maternal T cells in human severe combined immunodeficiency: evidence for a TH2 phenotype and a potential role of apoptosis on the restriction of T-cell receptor variable β repertoire J. Allergy Clin. Immunol. 1998 101 1 131 -134
Poliani P.L., Facchetti F., Ravanini M., Gennery A.R., Villa A., Roifman C.M., and Notarangelo L.D. Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome Blood. 2009 114 1 105 -108
Pollack M.S., Kapoor N., Sorell M., Kim S.J., Christiansen F.T., Silver D.M., Dupont B., and O'Reilly R.J. DR-positive maternal engrafted T cells in a severe combined immunodeficiency patient without graft-versus-host disease Transplantation. 1980 30 5 331 -334
Pollack M.S., Kirkpatrick D., Kapoor N., Dupont B., and O'Reilly R.J. Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency N. Engl. J. Med. 1982 307 11 662 -666
Roifman C.M., Somech R., Kavadas F., Pires L., Nahum A., Dalal I., and Grunebaum E. Defining combined immunodeficiency J. Allergy Clin. Immunol. 2012 130 1 177 -183
Shearer W.T., Dunn E., Notarangelo L.D., Dvorak C.C., Puck J.M., Logan B.R., Griffith L.M., Kohn D.B., O'Reilly R.J., Fleisher T.A., Pai S.Y., Martinez C.A., Buckley R.H., and Cowan M.J. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience J. Allergy Clin. Immunol. 2014 133 4 1092 -1098
Somech R., Simon A.J., Lev A., Dalal I., Spirer Z., Goldstein I., Nagar M., Amariglio N., Rechavi G., and Roifman C.M. Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal T cells J. Allergy Clin. Immunol. 2009 124 4 793 -800
Tezcan I., Ersoy F., Sanal O., Turul T., Uckan D., Balci S., Hicsonmez G., Prieur M., Caillat-Zucmann S., Le Deist F., and de Saint Basile G. Long-term survival in severe combined immune deficiency: the role of persistent maternal engraftment J. Pediatr. 2005 146 1 137 -140
Thompson L.F., O'Connor R.D., and Bastian J.F. Phenotype and function of engrafted maternal T cells in patients with severe combined immunodeficiency J. Immunol. 1984 133 5 2513 -2517
Touzot F., Dal-Cortivo L., Verkarre V., Lim A., Crucis-Armengaud A., Moshous D., Héritier S., Frange P., Kaltenbach S., Blanche S., Picard C., Hacein-Bey-Abina S., Cavazzana-Calvo M., and Fischer A. Massive expansion of maternal T cells in response to EBV infection in a patient with SCID-Xl Blood. 2012 120 9 1957 -1959
Vaidya S., Mamlok R., Daeschner C.W. 3rd, Williams J., Ruth J., and Goldblum R.M. Suppression of graft-versus-host reaction in severe combined immunodeficiency with maternal-fetal T cell engraftment Am. J. Pediatr. Hematol. Oncol. 1991 13 2 172 -175
Villa A., Notarangelo L.D., and Roifman C.M. Omenn syndrome: inflammation in leaky severe combined immunodeficiency J. Allergy Clin. Immunol. 2008 122 6 1082 -1086
Villa A., Santagata S., Bozzi F., Giliani S., Frattini A., Imberti L., Gatta L.B., Ochs H.D., Schwarz K., Notarangelo L.D., Vezzoni P., and Spanopoulou E. Partial V(D)J recombination activity leads to Omenn syndrome Cell. 1998 93 5 885 -896
Information & Authors
Information
Published In
LymphoSign Journal
Volume 2 • Number 1 • March 2015
Pages: 47 - 52
History
Received: 17 September 2014
Accepted: 7 October 2014
Accepted manuscript online: 28 October 2014
Version of record online: 28 October 2014
Authors
Metrics & Citations
Metrics
Other Metrics
Citations
Cite As
Raz Somech. 2015. Self-reactive and transplacental-acquired maternal T cells in SCID patients—time to update. LymphoSign Journal.
2(1): 47-52. https://doi.org/10.14785/lpsn-2014-0017
Export Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
There are no citations for this item
View Options
Get Access
Login options
Check if you access through your login credentials or your institution to get full access on this article.
