The humoral response in TCR alpha-/- mice. Can gammadelta-T cells support the humoral immune response?
An optimal humoral response requires T-cell help; however, it has been questioned if this help comes exclusively from alphabeta-T cells or whether gammadelta-T cells also contribute. We have attempted to answer this question by studying the humoral response in T-cell receptor alpha-chain knockout (alpha-/-) mice, which lack the alphabetaT cell subset. Two model antigens were used to characterize the response: the thymus-independent (TI) antigen native dextran B512 (Dx), and the thymus-dependent (TD) antigen heat shock protein (HSP65) from Mycobacterium tuberculosis. When challenged with Dx, the alpha-/- mice elicited a strong antibody response and formed rudimentary germinal centres (GCs), a T-cell dependent reaction. In contrast, the humoral response to HSP65 was poor. However, alpha-/- mice became primed when challenged with HSP65, because when supplemented with wild-type thymocytes, the antigen-primed animals were able to mount a stronger response than the nonprimed ones when challenged with HSP65. A crucial step seems to be the collaboration between gammadeltaT cells and antigen presenting cells (APCs), as splenocytes from alpha-/- mice were able to respond to HSP65 in an environment containing primed-APCs. Based on these results, we propose a model for B-cell activation in the alpha-/- mice.
Lindroth
K
K
Department of Immunology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. karin.lindroth@imun.su.se
Troye-Blomberg
M
M
Singh
M
M
Dieli
F
F
Ivanyi
J
J
Fernández
C
C
D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D003911:Dextrans / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D001426:Bacterial Proteins; D018834:Chaperonin 60; D003911:Dextrans; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins