Reconstitution of C.B-17 scid mice with BALB/c T cells initiates a T helper type-1 response and renders them capable of healing Leishmania major infection.
C.B-17 scid mice, which were found to be very susceptible to infection with Leishmania major, were reconstituted with various doses of T cells, T plus B cells or unfractionated spleen cells from nonhealer BALB/c mice. All reconstitution protocols, except for the transfer of very high numbers of BALB/c spleen cells, led to a spontaneously healing infection and resistance to reinfection, rather than the lethal, nonhealing infection typical of BALB/c mice. These healing responses were associated with a strong T helper 1 (Th1)-like response characterized by delayed-type hypersensitivity (DTH) responsiveness, but no elevation of serum IgE, and by the production of high levels of interferon-gamma (IFN-gamma), but no interleukin-4 (IL-4) by lymph node and spleen cells after restimulation with antigen in vitro. The development of this Th1 response from BALB/c Th cells requires IFN-gamma during the initial infection period. Treatment of scid mice with a single injection of neutralizing anti-IFN-gamma antibody prior to infection and reconstitution prevented healing and permitted the development of a Th-2 like response as indicated by elevated serum IgE, but no DTH, and by the production of IL-4, but very little IFN-gamma, after antigen stimulation in vitro. As few as 10(4) transferred T cells led to a Th1-like response, suggesting that the IFN-gamma is of host rather than donor origin. The transfer of very high numbers (7.5 x 10(7)) of BALB/c spleen cells overcame the effects of the IFN-gamma and led to the nonhealing infection and cytokine pattern characteristic of BALB/c mice. The enrichment or depletion of B cells from the transferred T cells had no measurable effect upon the development of a healing response in reconstituted scid mice.
Varkila
K
K
Immunology Department, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, CA 94304-1104.
Chatelain
R
R
Leal
L M
LM
Coffman
R L
RL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D007895:Leishmania tropica; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D013154:Spleen / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma