Nude mice are not resistant to xenograft due to the absence of ________________

Correct Answer: C. T cell

Nude mice (athymic mice) lack a functional thymus gland, resulting in severe T cell deficiency while retaining relatively intact B cell and NK cell populations. Xenograft rejection is primarily a T cell-mediated (cellular) immune response. The rejection occurs through two main mechanisms: (1) direct recognition of foreign MHC molecules on donor cells by host CD8+ cytotoxic T lymphocytes (CTLs), and (2) indirect recognition where host antigen-presenting cells process and present donor antigens to host CD4+ T helper cells, activating both cellular and humoral responses. Without functional T cells, nude mice cannot mount this critical cell-mediated rejection response, making them permissive hosts for xenografts. B cells alone (producing antibodies) and NK cells (innate immunity) are insufficient to reject xenografts in the absence of T cell help and coordination. This is why nude mice are routinely used in research to establish human tumor xenografts and study xenograft biology without immunological rejection complications. The absence of T cells is the discriminating factor that explains xenograft acceptance in these immunocompromised animals.

Why the other options are wrong

A. Both B and T cell — While T cell absence is the critical factor, nude mice retain functional B cells and NK cells. If both B and T cells were absent, the answer would be incomplete and misleading. The question specifically tests understanding that T cells are the PRIMARY mediator of xenograft rejection. Choosing this option suggests confusion about which arm of immunity is responsible for xenograft rejection. B. NK cell — NK cells are part of innate immunity and play a minor role in xenograft rejection compared to T cells. Nude mice retain functional NK cells despite lacking T cells, yet they still accept xenografts readily. This is an NBE trap—students may confuse NK cell importance in general immunosurveillance with their actual role in xenograft rejection, which is secondary to T cell-mediated responses. D. B cell — Nude mice retain functional B cells and antibody production. While B cells contribute to xenograft rejection through complement-dependent cytotoxicity and ADCC, they require T cell help (CD4+ T cells) for optimal antibody responses. B cell deficiency alone does not explain xenograft acceptance in nude mice, as T cell-mediated rejection is the dominant mechanism.

High-Yield Facts

Mnemonics

NUDE = No Thymus = No T cells Nude mice → athymic → T cell deficiency. Remember: the thymus is the T cell factory. No thymus = no T cells. Use this when identifying why nude mice accept xenografts. XenoREJECT = T cell REJECTs foreign MHC Xenograft rejection requires T cells recognizing foreign MHC (direct) or processed antigens (indirect). T cells are the gatekeepers of xenograft immunity. B and NK cells are supporting players, not the main actors.

NBE Trap

NBE pairs "nude mice" with "immunodeficiency" to lure students into choosing "Both B and T cell" or "NK cell." The trap is forgetting that nude mice retain B and NK cells—the question specifically tests whether you know that T cells are the CRITICAL missing component for xenograft rejection, not a general immunodeficiency state.

Clinical Pearl

In Indian research institutions, nude mice are extensively used to establish patient-derived xenografts (PDX) from Indian cancer patients for drug testing and personalized oncology studies. The absence of T cell-mediated rejection allows human tumors to engraft and grow in these mice, enabling preclinical evaluation of novel therapeutics before human trials—a critical step in translational cancer research in India.

_Reference: Jawetz, Melnick & Adelberg's Medical Microbiology (Ch. Immunology & Host Defenses); Robbins & Cotran Pathologic Basis of Disease (Ch. Neoplasia - Xenograft models)_