CD2 expression correlates with proliferative capacity of alpha beta + or gamma delta + CD4-CD8- T cells in lpr mice.
The T lymphocytes that accumulate in vast numbers in the lymphoid tissues of lpr/lpr (lpr) mice express a TCR-alpha beta that is polyclonally rearranged, and yet is devoid of surface CD4 or CD8 (CD4-8-) as well as CD2. lpr CD2- alpha beta + CD4-8- T cells exhibit an apparent block in signal transduction, in that when activated they produce little or no IL-2 and proliferate minimally in the absence of exogenous IL-2. In contrast to the predominant hyporesponsive alpha beta + CD4-8- T cells, we observe that a minor subset (1 to 2%) of lpr lymph node CD4-8- cells expresses a TCR-gamma delta and can proliferate upon activation with PMA and ionomycin in the absence of exogenous IL-2. Furthermore, these responsive gamma delta T cells express surface CD2. The functional and phenotypic distinctions of lpr gamma delta T cells led us to identify an analogous minor (4 to 10%) subset of alpha beta + CD4-8- cells in lpr thymus and lymph nodes that does express CD2. Similar to the gamma delta subset, these CD2+ alpha beta + CD4-8- cells are also capable of proliferation and IL-2 production. Thus the capacity for IL-2 production and proliferation by a small proportion of lpr CD4-8- T cells, either alpha beta + or gamma delta +, correlates with their expression of surface CD2. This correlation is supported by the observation that the lpr liver contains actively cycling alpha beta + CD4-8- lymphocytes that are strikingly enriched for CD2 expression. Consequently, unlike the vast proportion of abnormal lpr CD2- CD3+ CD4-8- cells, the CD2+ CD3+ CD4-8- T cells may not express the basic lpr defect, or else are not affected by its presence. These studies suggest that expression of the lpr abnormality may be restricted to a particular T cell lineage. This functional correlation with CD2 expression may be more broadly applicable to phenotypically similar subsets of normal thymocytes, and possibly peripheral tolerized T lymphocytes.
Budd
R C
RC
Rheumatology and Clinical Immunology Unit, University of Vermont College of Medicine, Burlington 05405.
Russell
J Q
JQ
van Houten
N
N
Cooper
S M
SM
Yagita
H
H
Wolfe
J
J
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001327:Autoimmune Diseases / Q000276:immunology*; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D006649:Histocompatibility Antigens / Q000032:analysis; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D017493:Leukocyte Common Antigens